Method for preparing gel with calcium salts of organic acids

ABSTRACT

A method for preparing a gel composition, such as alginate gel beads, using a proper concentration of calcium pantothenate or calcium ascorbate as a gelling agent.

This application is a 371 of International Application No.PCT/JP98/02823, filed on Jun. 24, 1998, which, in turn, claims thebenefit of Japanese Application No. 9/283,789, filed Oct. 16, 1997.

TECHNICAL FIELD

This invention relates to gelling agents and a method for preparinggels.

BACKGROUND ART

Calcium chloride or the like is usually used as a gelling agent toprepare gel compositions such as an alginate gel or others. However,when calcium chloride or the like is used as a gelling agent, it isnecessary to remove the gelling agent by washing after the gel isprepared, which raises a problem of the loss of active ingredients inthe gel by the washing process. Accordingly, more efficient gellingmethods that do not require the washing for the removal of the gellingagent have been awaited in this technical field.

Calcium pantothenate is a member of the vitamin-B group, water-solublevitamins. Pantothenic acid is a component of coenzyme A and participatesin acyl group transfer in vivo, playing important roles in themetabolism of lipids and carbohydrates. The lack of this vitamin causesdisorders of the skin, adrenal gland, peripheral nerves, digestivetracts, antibody production, reproductive function, etc. Calciumascorbate is a member of the vitamin-C group, water-soluble vitamins.Calcium ascorbate is absorbed in the digestive tracts and widelydistributed over tissues in the body in the form of ascorbic acid, whichhas an antiscorbutic activity, promotes platelet production, andsuppresses melanogenesis. The lack of ascorbate results in the vitamin Cdeficiency (scurvy, etc.).

Calcium pantothenate and calcium ascorbate are currently widely used forfodders, health foods, and pharmaceuticals, etc. However, there are noreports on the applicability of these compounds as a gelling agent.

DISCLOSURE OF THE INVENTION

An objective of the present invention is to provide a more effectivegelling agent and a method for preparing gel using the gelling agent.The present inventors investigated the applicability of calciumpantothenate, a member of the vitamin-B group, or calcium ascorbate, amember of the vitamin-C group, to a gelling agent, specifically, forpreparing alginate gel beads. Eventually, it was found that the gel wasformed-by using the calcium salts of these acids at a suitableconcentration, and thus the present invention was completed.

Namely, this invention relates to a method for preparing a gelcomposition utilizing a calcium salt of an acid as a gelling agent, morespecifically, to:

(1) a method for preparing a gel composition, the method comprisingusing a calcium salt of an organic acid as a gelling agent;

(2) the method as described in (1), wherein the organic acid calciumsalt is calcium pantothenate or calcium ascorbate;

(3) the method as described in (1), wherein the gel composition isalginate gel composition;

(4) the method as described in (1), wherein the gel composition containschitosan or a salt thereof;

(5) a gel composition comprising calcium pantothenate or calciumascorbate, which is obtainable in a single-step process of gel formationby mixing an aqueous solution of a substance having gelling capabilityand an aqueous solution of calcium pantothenate or calcium ascorbate;

(6) the gel composition as described in (5), wherein the organic salt isselected from the group consisting of lactic acid, ascorbic acid,gluconic acid, and citric acid;

(7) the gel composition as described in (5), wherein the substancehaving gelling capability is sodium alginate.

A calcium salt of an organic acid for preparing gel compositions used inthe present invention is not particularly limited, but preferablycalcium pantothenate or calcium ascorbate.

Calcium pantothenate may be isolated from natural sources such asyeasts, the liver, and others, or may be chemically synthesized by, forexample, the condensation reaction of a calcium salt of β-alanine andpantolactone to yield calcium d(+)-pantothenate (M. Catzi-Fichter: Helv.Chem. Acta., 24, 185 (1941)). In addition, pantothenic acid is known tobe biosynthesized by enteric bacteria in mammals, and by yeasts,Escherichia coli and Neurospora crassa through the condensation ofD-pantoic acid and β-alanine in the presence of ATP (W. K. Mass, Proc.4th Int. Congr. Biochem., Vol.11, p.161, Pergamon Press, London (1960)).Pantothenic acid used in the present invention can be synthesized by anyof enzymes involved in such biosynthetic reactions. It can also beproduced with a bioreactor using microorganisms such as yeasts,Escherichia coli, and Neurospora crassa mentioned above. There exist theD-enantiomer and L-enantiomer of pantothenic acid. Both calciumD-pantothenate and calcium L-pantothenate can be used as calciumpantothenate used in the present invention. Since the L-enantiomer doesnot possess the activity as the vitamin, the D-enantiomer should be usedwhen the vitamin activity is required besides the function as a gellingagent.

Calcium ascorbate may be naturally occurring or chemically synthesizedones. The commercial product (Takeda Chemical Industries, Ltd.) can alsobe used. Ascorbic acid can be the D-enantiomer and L-enantiomer. Bothcalcium D-ascorbate and calcium L-ascorbate can be used as calciumascorbate used in the present invention. The D-enantiomer does notpossess the activity as the vitamin, and therefore the L-enaniomershould be used when the vitamin activity is required besides thefunction as a gelling agent.

A substance having gelling capability used in the method of thisinvention includes, for example, sodium alginate, pectin, carrageenan,agar, and gelatin. Any other substances that are gelled by calcium canbe used in the method of this invention.

Chitosan used for preparing gel compositions in this invention includeschitosan having the glucosamine residue content (the degree ofdeacetylation) in its sugar chain of about 60% or more and averagemolecular weight of about 1500 to about 400,000.

When sodium alginate is used as the substance having gelling capability,a gel preparation can be produced using calcium pantothenate or calciumascorbate by adding a 0.1 to 10% sodium alginate aqueous solution or anaqueous sodium alginate solution containing 1 to 10% chitosan dropwiseto a aqueous solution of calcium pantothenate or calcium ascorbate, or asolution containing one of these calcium salts and 1 to 10% organic acid(for example, lactic acid, ascorbic acid, and gluconic acid, etc.) toform instantaneously alginate gel beads or chitosan salt-containingalginate gel beads. The concentration of calcium pantothenate used inthis preparation ranges usually from about 0.03M to about 0.4M. The pHof the reaction system ranges usually from about 4.5 to about 7.0, andpreferably about 6.0 to about 7.0. Calcium ascorbate is used in aconcentration of about 0.02M to about 0.2M, and preferably about 0.1 toabout 0.2M. The pH of the reaction system ranges usually from about 4.0to about 7.0, and preferably about 4.5 to about 6.5. When a substanceother than alginate gel is used as the substance having gellingcapability, the pH in the reaction system should be adjusted so as notto inhibit the gel formation, preferably ranges from acidic to neutralpH.

Substances other than described above can be incorporated in thecomposition prepared by the method of this invention upon gellation. Thesubstance to be incorporated is dissolved or suspended in a solution ofalginic acid in advance, then can be easily trapped in the gel beads.The substance to be incorporated is not particularly liminted as long asit is solid or liquid. The method of this invention is advantageouslyapplicable to substances that are decomposed by thermolysis andtherefore are hardly incorporated in the gel such as agar by theconventional method. For example, multivitamin preparations can beprepared by incorporating other vitamins in the gel. When water-solublevitamins is to be incorporated, the method of this invention isextremely advantageous in that the washing procedure to remove thegelling agent is not required. Incorporation of a chitosan salt capableof trapping taurocholic acid confers lipid metabolism-improving functionon the gel preparation.

When cholestyramine, which causes constipation as the side effect, isincorporated, use of calcium pantothenate as a gelling agent cancompensate the side effect of cholestyramine due to its ability torelieve constipation. Thus, the method of this inveniton is suitablyapplied to the manufacture of multivitamin preparations for improvinglipid metabolism and vitamin-containing functional foods, whichameliorates atonic constipation. Moreover, ascorbic acid is known toreduce the cholesterol level, and accordingly, the method of thisinvention using calcium ascorbate as a gelling agent is suitably appliedto the manufacture of pharmaceutical preparations or functional foodsfor treating hyperlipemia.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graph showing the contents of pantothenic acid in chitosanlactate-containing or chitosan lactate-free alginate gel beads.

FIG. 2 is a graph showing the contents of pantothenic acid plottedagainst the concentration of calcium pantothenate used as a gellingagent.

FIG. 3 is a graph showing the time-dependent pantothenic acid-releasingbehavior of chitosan lactate-containing or chitosan lactate-freealginate gel beads.

FIG. 4 is a graph showing the uptake of taurocholic acid by chitosanlactate-containing or chitosan gluconate-containing alginate gel beads.

FIG. 5 is a graph showing the influence of the calcium pantothenateconcentration at the time of gellation on the uptake of taurocholic acidby chitosan lactate-containing alginate gel beads.

FIG. 6 is a graph showing the influence of the incubation time forpreparing chitosan lactate-containing alginate gel beads on the uptakeof taurocholic acid by the gel beads.

FIG. 7 shows the difference in the uptake of taurocholic acid by the gelbeads prepared by method A (Example 2(1)) using 0.1% ascorbic acid (AA)or calcium ascorbate (Asc-Ca) as a weak acid.

FIG. 8 shows the uptake of taurocholic acid by the gel beads prepared bymethod A using 0.1 or 0.2% ascorbic acid (AA) as a weak acid.

FIG. 9 shows the uptake of taurocholic acid by the dry gel beadsprepared by method A using 0.05, 0.1, or 0.2% ascorbic acid (AA) as aweak acid.

FIG. 10 shows the time-course of the influence of ascorbic acid (AA),sodium ascorbate (Asc-Na), or calcium ascorbate (Asc-Ca) added to ataurocholic acid solution on the uptake of taurocholic acid by therespective gel beads prepared by method A.

FIG. 11 shows the uptake of taurocholic acid by the gel beads preparedby method B (Example 2(2)) using 0.02 to 2 M calcium ascorbate (Asc-Ca)as a gelling agent and 1% ascorbic acid (AA) as a weak acid.

FIG. 12 shows the relationship between the pH and the amount of calciumascorbate in method B using 1% ascorbic acid (AA) as a weak acid.

FIG. 13 shows the uptake of taurocholic acid by the gel beads preparedby method B using 0.02 M calcium ascorbate (Asc-Ca) as a gelling agentand 1% ascorbic acid (AA) as a weak acid. The treatment with ascorbicacid (AA) was continued for 2 hours or 1 day.

FIG. 14 shows the uptake of taurocholic acid by the gel beads preparedby method C (Example 2(3)) using 0.02 M calcium ascorbate (Asc-Ca) as agelling agent and 0.2% ascorbic acid (AA) as a weak acid. The treatmentwith the weak acid was continued for 1, 3 or 5 days.

FIG. 15 shows the structural change of ascorbic acid in hydro-gel beadsprepared by method C.

FIG. 16 shows the uptake of taurocholic acid by the gel beads preparedby method C using 0.02 M calcium ascorbate (Asc-Ca) as a gelling agentand, as weak acids, ascorbic acid (AA) and citric acid (CA) in variouscombinations of their concentrations.

FIG. 17 shows the uptake of taurocholic acid by the gel beads preparedby method C using 0.02 M calcium ascorbate (Asc-Ca) as a gelling agentand ascorbic acid (AA) and citric acid (CA) as weak acids.

BEST MODE FOR CARRYING OUT THE INVENTION

The present invention will be described below in detail with referenceto the following examples, but is not to be construed as being limitedthereto. The materials used in Examples 1 and 2 were obtained from thefollowing suppliers: chitosan (Kimitsu Chemical Industries Ltd., GradeF, the degree of deacetylation: 75-85%); alginic acid (NAKALAI TESQUE,INC., 500 cps); ascorbic acid (Wako Pure Chemical Industries Ltd.,special grade).

EXAMPLE 1 Preparation of Alginate Gel Beads Using Calcium Pantothenateas a Gelling Agent

(1) Pantothenic acid content in various alginate gel beads

Alginate gel beads were formed by adding dropwise 2.0 g of achitosan-free or 5% chitosan-containing 1% sodium alginate solution to10 ml of 0.2M calcium pantothenate solution containing 1% lactic acidand incubating the mixture at 37° C. for 3 hours. Subsequently,pantothenic acid was separated from various alginate gel beads obtainedand quantitatively measured by ion-pair chromatography using HPLC. HPLCwas performed using COSMOSIL 5C-18-MS (4.6×150 mm) column and 5 mMtetrabutylammonium phosphate:methanol=3:1 as an eluate at the flow rateof 1.0 ml/minute. Detection was carried out at the wave length of 254nm.

As shown in FIG. 1, the content of pantothenic acid was 203 μmol in thechitosan-free dry gel beads, 529 μmol in the chitosan-containinghydro-gel beads, 476 μmol in the chitosan-containing dry gel beads.Thus, the content of pantothenic acid was higher in the chitosansalt-containing alginate gel beads than in the chitosan salt-freealginate gel beads.

(2) Relationship between the pantothenic acid content in alginate gelbeads and the calcium pantothenate concentration used for gelpreparation

Chitosan salt-embedded alginate gel beads were formed by the same methoddescribed in (1). The relationship between the calcium pantothenateconcentration and the pantothenic acid content in the alginate gel beadswas investigated, varying the calcium pantothenate concentration to0.05M, 0.1M, 0.15M, 0.2M, and 0.25M. The pantothenic acid content in thealginate gel beads was measured by the same method as described in (1).As can be seen in FIG. 2, the pantothenic acid content in the alginategel beads was increased depending on the calcium pantothenateconcentration used for gel preparation.

(3) Releasing behavior of pantothenic acid from the alginate gel beads

The content of pantothenic acid released from the alginate gel beadsprepared by the same method as described in (1) was measured with thepassage of time. The measurement was carried out by HPLC or ONPH. HPLCwas performed using COSMOSIL 5C-18-MS (4.6×150 mm) column and 5 mMtetrabutylammonium phosphate:methanol=3:1 as an eluate at the flow rateof 1.0 ml/minute. Detection was performed with a UV detector. The ONPHmethod was performed by adding 1 ml of a 0.41N hydrochloric acidsolution containing 10 mM ONPH·HCl to 2 ml of a sample, further adding 1ml of a 4% (v/v) pyridine solution containing 0.15M carbodiimide (EDC)thereto, and incubating the mixture at 40° C. for 30 minutes. Then, 1 mlof 1.5N NaOH was added to the reaction mixture, which was incubated at60° C. for 15 minutes, followed by detection using a spectrometer.

The results are shown in FIG. 3. When measured by HPLC, more pantothenicacid was released from the chitosan-containing gel beads than from thechitosan-free gel beads. The amount of pantothenic acid released fromthe chitosan-free gel beads measured by ONPH almost agreed with thatmeasured by HPLC.

(4) Uptake of taurocholic acid by various chitosan salt-embeddedalginate gel beads

The chitosan salt-embedded alginate gel beads were formed by the samemethod as described in (1), except for using 2% gluconic acid, 4%gluconic acid, or 1% lactic acid as a weak acid. The dry gel beads(about 50 mg in dry weight) prepared by the method described in (1) wereadded to 15 ml of 2 mM taurocholic acid solution in a L-shaped tube.While the tube was shaken at 67 rpm at 37° C., aliquots of the aqueoussample were taken with the passage of time, and the amount oftaurocholic acid in the system was measured by HPLC. HPLC was performedusing COSMOSIL 5C-18-MS (4.6×150 mm) column and methanol:30 mM phosphatebuffer (pH 3.4):acetonitrile=6:3:1 as an eluate at the flow rate of 0.8ml/minute. Detection was carried out at the wave length of 235 nm. Theresult is shown in FIG. 4. As shown in FIG. 4, sufficient uptake oftaurocholic acid was observed in the gel beads prepared using gluconicacid or lactic acid as a weak acid. Uptake of taurocholic acid was lessby the gel beads prepared using 2% gluconic acid than by those preparedusing 4% gluconic acid up to about 70 minutes from the initiation of themeasurement, whereas the oppposite result was obtained after 100 minutesfrom the initiation of the measurement.

(5) Effect of the calcium pantothenate concentration at the time of gelpreparation on uptake of taurocholic acid by the chitosansalt-containing alginate gel beads

The chitosan salt-containing alginate gel beads were formed by the samemethod as described in (1), except for varying the calcium pantothenateconcentration to 0.05M, 0.1M, 0.15M, 0.2M, and 0.25M. The effect of thecalcium pantothenate concentration at the time of gel preparation on thetaurocholic acid uptake by the chitosan salt-containing alginate gelbeads was investigated by measuring in the course of time thetaurocholic acid uptake by the chitosan-containing alginate gel beads inthe same manner as in (4). No influence of the calcium pantothenateconcentration at the time of gel preparation on the taurocholic aciduptake by the chitosan salt-containing alginate gel beads was observedas shown in FIG. 5.

(6) Effect of the time required for preparing the alginate gel beads onthe taurocholic acid uptake by the chitosan salt-immobilized gel beads

The chitosan salt-embedded alginate gel beads were prepared by the samemethod as described in (1) except for varying the incubation time to 3hours, 8 hours, and 24 hours. The effect of the gel preparation time onthe taurocholic acid uptake by the gel beads was investigated bymeasuring in the course of time the taurocholic acid uptake in the samemanner as in (4). As shown in FIG. 6, almost no influence of the timerequired for the gel preparation on the taurocholic acid uptake by thechitosan salt-immobilized alginate gel beads was observed.

EXAMPLE 2 Preparation of Alginate Gel Beads Using Ascorbate Calcium as aGelling Agent

(1) Method for preparing alginate gel beads containing ascorbic acid andchitosan(method A) and the taurocholic acid uptake by the gel beads

The alginate gel beads were formed by adding 2.0 g of 1% sodium alginatesolution containing 5% chitosan to 10 ml of 0.1M or 0.2M calciumascorbate solution and incubating the mixture at room temperature for 2hours. The thus-obtained alginate gel beads were added to 500 ml of aweak acid solution. The mixture was allowed to stand at room temperaturefor 24 hours to embed the chitosan salt in the gel. The hydro-gel beadswere thus obtained. The hydrogel beads were dried to prepare the dry gelbeads (method A).

The hydro-gel beads were prepared by method A using 0.1% ascorbic acidas a weak acid or using 0.1% sodium ascorbate, and the taurocholic aciduptake by the hydro-gel beads was examined. The hydro-gel beads (2 g)were added to the L-shaped tube containing 15 ml of a 2 mM taurocholicacid aqueous solution. While the tube was shaken at 67 rpm at 37° C.,the mixture was sampled from the tube with the passage of time, and thetaurocholic acid in the system was measured by HPLC to determine thetaurocholic acid uptake. HPLC was performed using COSMOSIL 5C-18-MS(4.6×150 mm) column and methanol:30 mM phosphatebuffer:acetonitrile=6:3:1 as an eluate at the flow rate of 0.8ml/minute. Detection was carried out at the wave length of 235 nm. Theresult showed that sufficient taurocholic acid uptake was detected whenascorbic acid was used as a weak acid, while no significant uptake oftaurocholic acid was detected by the gel beads prepared using sodiumascorbate (FIG. 7). The same experiment was performed using thehydro-gel beads prepared by using 0.1% ascorbic acid and 0.2% ascorbicacid as a weak acid. No significant difference was detected in thetaurocholic acid uptake by the two gels (FIG. 8).

In addition, the dry gel beads were prepared by method A using 0.05,0.1, and 0.2% ascorbic acid as a weak acid. The taurocholic acid uptakeby the resulting dry gel beads was measured by the same method asdescribed above. As a result, no significant difference was detected inthe taurocholic acid uptake by the gel beads prepared using ascorbicacid with a concentration of 0.1% or higher (FIG. 9).

To analyze the influence of solvents on the taurocholic acid uptake, 5%ascorbic acid or 0.15 ml of salts thereof was added to 15 ml of ataurocholic acid solution in a L-shaped tube, and the mixture was shakenat 37° C. The time-course change of the amount of taurocholic acid wasmonitored. No change of the taurocholic acid amount was detected (FIG.10).

(2) Method for preparing the alginate gel beads containing both ascorbicacid and chitosan (method B) and the taurocholic acid uptake by the gelbeads

The hydro-gel beads were prepared by adding 2.0 g of a 1% sodiumalginate solution containing 5% chitosan to 10 ml of a calcium ascorbatesolution containing a weak acid and incubating the mixture at 37° C. for2 hours to embed chitosan salt in the gel. The hydro-gel beads weredried to prepare the dry gel beads (method B). This method does notrequire to wash the gel with a large volume of a weak acid, and is thusindustrially advantageous.

Gel beads were prepared using 0.02 to 0.2 M calcium ascorbate as agelling agent and 1% ascorbic acid as a weak acid, and the taurocholicacid uptake by the gel beads was measured by the same method asdescribed in Example 2 (1). As a result, sufficient taurocholic aciduptake was observed when calcium ascorbate was used in a concentrationof 0.02 M, 0.03 M, or 0.05 M (FIG. 11).

Subsequently, the relationship between the amount of calcium ascorbateadded as a gelling agent and the pH of the system when 1% ascorbic acidwas used as a weak acid was assessed. The result is shown in FIG. 12.Chitosan ascorbate was formed in the ascorbic acid-calcium ascorbatebuffer (about pH 4 to 5). Thus, lower pHs in the system are advantageousin the chitosan-salt formation, and more taurocholic acid molecules canbe taken by the resulting gel (FIG. 11).

Next, the hydro-gel beads were prepared by method B using 0.02 M calciumascorbate as a gelling agent and 1% ascorbic acid as a weak acid andincubating the system with the ascorbic acid for 2 hours or 1 day. Therelationship between the period of the ascorbic acid treatment and thetaurocholic acid uptake was assessed. No significant difference wasobserbed between the 2-hour and 1-day treatments (FIG. 13).

(3) Method for preparing the alginate gel beads containing ascorbic acidand chitosan (method-C) and the taurocholic acid uptake by the gel beads

The alginate gel beads were prepared by adding 2.0 g of a 1% sodiumalginate solution containing 5% chitosan to 10 ml of a calcium ascorbatesolution and incubating the mixture at 37° C. for 2 hours. The obtainedalginate gel beads were then added to 90 ml of a weak acid solution, themixture was allowed to stand at room temperature for 24 hours, and thechitosan salt was allowed to be embeded in the gel to prepare thehydro-gel beads. The hydro-gel beads were dried to prepare the dry gelbeads (method C).

The hydro-gel beads were prepared using 0.02 M calcium ascorbate as agelling agent and 0.2% ascorbic acid as a weak acid and incubating thesystem with the weak acid for 1 day, 3 days or 5 days, and thetaurocholic acid uptake was examined. In any treating time, sufficienttaurocholic acid uptake was observed (FIG. 14).

The structural change of ascorbic acid in the prepared hydro-gel beadswas also assessed to confirm that the activity of ascorbic acid asvitamin C was not decreased due to its decomposition or degenerationwhen preserved in an aqueous solution containing the alginate gel beads.The total amount of ascorbic acid was determined by theDinitrophenylhydrazine method (J. H. Roe, et al., J. Biol. Chem. 174,201 (1948)). Reduced ascorbic acid was detected using F kit(Boerhinger-Mannheim). As a result, there observed no significantdifference in the total amount of ascorbic acid due to the variedweak-acid treatment time, while the amount of reduced ascorbic acid wasdecreased in the samples treated with the weak acid for 3 days or 5 days(FIG. 15).

Next, the hydro-gel beads were prepared using 0.02 M calcium ascorbateas a gelling agent and using as a weak acid a mixture of ascorbic acidand citric acid that is used as an additive for drinks, varying themixing ratio. The gels were treated with the weak acid mixture for 1day, and the taurocholic acid uptake was assayed. The result revealedthat the most excellent taurocholic acid uptake was observed with thegel beads that were treated with a combination of 0.5% ascorbic acid and0.5% citric acid or in a combination of 1.0% ascorbic acid and 0.1%citric acid (FIG. 16).

Separately, the dry gel beads were prepared by method C using 0.02 Mcalcium ascorbate as a gelling agent, in which the gels were treatedwith a mixture of ascorbic acid and citric acid as a weak acid for 1day. The taurocholic acid uptake was assayed. As a result, sufficienttaurocholic acid uptake was observed by the dry gel beads treated with acombination of 0.5% ascorbic acid and 0.5% citric acid or a combinationof 0.2% ascorbic acid and 0.2% citric acid (FIG. 17).

Industrial Applicability

The present invention provides a method for preparing gel using acalcium salt of an acid as a gelling agent. The method of this inventiondoes not require washing for removing a gelling agent after thepreparation of gel, and thus is an extremely efficient method.

When calcium pantothenate or calcium ascorbate is used as a gellingagent, the gel prepared using it can be a useful vitamin preparationbecause these calcium salts originally function as vitamins and they arereleased from the gel after taken.

Furthermore, calcium pantothenate or calcium ascorbate might play usefulroles by cooperating with a substance embedded in the gel. For example,when cholestyramine, an anti-hyperlipemia drug, is embedded in the gel,calcium pantothenate that enhances the intestinal motility can reduceconstipation caused by cholestyramine as the side effect. Ascorbic acidis known to lower the blood-cholesterol level, and, when cholestyramineis embedded in the gel prepared using ascorbate as a gelling agent, theprepared gel can be suitable as a pharmaceutical preparation orfunctional food for treating hyperlipemia.

The method of this invention also enables embedding other substances inthe gel. For example, multivitamin preparations can be prepared byembedding other vitamins. Furthermore, since the chitosan salt-embeddedgel takes up taurocholic acid, it can be used as a pharmaceuticalpreparation for improving lipid metabolism.

What is claimed is:
 1. A method for preparing a gel composition for oraladministration, the method comprising mixing a first aqueous solutioncomprising a substance having a gelling capability, with a secondaqueous solution comprising a gelling agent selected from the groupconsisting of (a) calcium pantothenate and an organic acid, and (b)calcium ascorbate.
 2. The method of claim 1, wherein the second aqueoussolution further comprises an organic acid when the gelling agent iscalcium ascorbate.
 3. The method of claim 1, wherein the gel compositionis alginate gel composition.
 4. The method of claim 3, wherein the gelcomposition further contains chitosan or a salt thereof.
 5. The methodaccording to claim 1, wherein the organic acid is selected from thegroup consisting of lactic acid, ascorbic acid, gluconic acid, andcitric acid.
 6. A gel composition for oral administration comprisingcalcium pantothenate or calcium ascorbate, which is obtainable in asingle-step process of gel formation by mixing an aqueous solution of asubstance having gelling capability with and an aqueous solutioncomprising (i) calcium pantothenate or calcium ascorbate and (ii) anorganic acid.
 7. The gel composition of claim 6, wherein the organicsalt is selected from the group consisting of lactic acid, ascorbicacid, gluconic acid, and citric acid.
 8. The gel composition of claim 6,wherein the substance having gelling capability is sodium alginate. 9.The gel composition of claim 6, wherein said gel composition comprises avitamin, food supplement, or pharmaceutical preparation.
 10. The gelcomposition of claim 6, wherein said gel composition further includes apharmaceutically active agent embedded therein.
 11. The gel compositionof claim 10, wherein said pharmaceutically active agent ischolestyramine.
 12. The gel composition of claim 11, wherein saidsubstance having gelling capability is calcium pantothenate, furtherwherein said gel composition reduces constipation caused bycholestyramine by enhancing intestinal motility.
 13. The gel compositionof claim 11, wherein said substance having gelling capability is calciumascorbate, further wherein said gel composition reduces bloodcholesterol levels.
 14. The gel composition of claim 6, wherein said gelcomposition further contains chitosan or a salt thereof, wherein saidgel composition improves lipid metabolism.